| Preclinical antitumor activity of a nanoparticulate SN38. | |
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MedLine Citation:
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PMID: 23299391 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The present studies were carried out to examine the efficacy of a nanoparticulate formulation of SN38, the potent topoisomerase I inhibitor and active metabolite of irinotecan. Metabolism of irinotecan to SN38 is inefficient and subject to considerable patient-to-patient variability. One approach to more controlled administration of the anticancer agent is direct administration of the active SN38. A nanoparticulate formulation of SN38 was prepared by a method of precipitation with compressed antisolvent. Nanoparticulate SN38 efficiently inhibited the proliferation of colorectal, ovarian, and mesothelial cancer cell lines in vitro. Concentrations resulting in 50 % inhibition of proliferation were approximately 1000 fold lower for nanoparticulate SN38 compared to irinotecan. In vivo effects were examined using colorectal and ovarian mouse model systems. In a mouse model of peritoneally disseminated ovarian cancer intraperitoneal administration of irinotecan was favorable to intravenous delivery however intraperitoneal delivery of nanoparticulate SN38 was significantly more effective than intraperitoneal irinotecan. In addition, in a mouse colorectal cancer model administration of nanoparticulate SN38 once weekly exhibited greater activity compared to daily or weekly administration of irinotecan. Additional studies demonstrated nanoparticulate SN38 administered as a combination therapy with mitomycin C was more effective than the combination of irinotecan and mitomycin C. Results from the present studies using preclinical colorectal and ovarian cancer model systems demonstrate the efficacy of nanoparticulate SN38 and substantiate continued development. |
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Authors:
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Mazin F Al-Kasspooles; Stephen K Williamson; David Henry; Jahna Howell; Fengui Niu; Charles J Decedue; Katherine F Roby |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-9 |
Journal Detail:
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Title: Investigational new drugs Volume: - ISSN: 1573-0646 ISO Abbreviation: Invest New Drugs Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309330 Medline TA: Invest New Drugs Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Surgery, University of Kansas Medical Center, Kansas City, KS, 66160, USA. |
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Descriptor/Qualifier:
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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